Hypokalemia has been reported in about 5% of hospitalized patients. Abnormalities in potassium have many similarities to those of sodium. Some conditions with potassium abnormalities are also associated with sodium abnormalities and were discussed earlier. Several different mechanisms may be involved.

Inadequate intake. Ordinarily, 90% of ingested potassium is absorbed, so that most diets are more than adequate. Inadequate intake is most often due to anorexia nervosa or to severe illness with anorexia, especially when combined with administration of potassium-free therapeutic fluids. Alcoholism is often associated with inadequate intake, and various malabsorption syndromes may prevent adequate absorption.

Gastrointestinal tract loss. Severe prolonged diarrhea, including diarrhea due to laxative abuse, can eliminate substantial amounts of potassium. One uncommon but famous cause is large villous adenomas of the colon.

Clinical Conditions Commonly Associated With Serum Potassium Abnormalities

Hypokalemia

Inadequate intake (cachexia or severe illness of any type)
Intravenous infusion of potassium-free fluids
Renal loss (diuretics; primary aldosteronism)
GI loss (protracted vomiting; severe prolonged diarrhea; GI drainage)
Severe trauma
Treatment of diabetic acidosis without potassium supplements
Treatment with large doses of adrenocorticotropic hormone; Cushing’s syndrome
Cirrhosis; some cases of secondary aldosteronism

Hyperkalemia

Renal failure
Dehydration
Excessive parenteral administration of potassium
Artifactual hemolysis of blood specimen
Tumor lysis syndrome
Hyporeninemic hypoaldosteronism
Spironolactone therapy
Addison’s disease and salt-losing congenital adrenal hyperplasia
Thrombocythemia

Protracted vomiting is another uncommon cause. Patients with ileal loop ureteral implant operations after total cystectomy frequently develop hypokalemia if not closely watched.

Renal loss. Twenty percent to 30% (range, 10%-40%) of hypertensive patients receiving diuretic therapy, particularly with the chlorothiazides, are reported to be hypokalemic. Combined with other conditions requiring diuretics, this makes diuretic therapy the most frequent overall cause of hypokalemia. Renal tubular acidosis syndromes might also be mentioned. Finally, there is a component of renal loss associated with several primarily nonrenal hypokalemic disorders. These include the various endocrinopathies (discussed next), diabetic ketoacidosis, and administration of potassium-poor fluids. The kidney is apparently best able to conserve sodium and to excrete potassium (since one way to conserve sodium is to excrete potassium ions in exchange), so that when normal intake of potassium stops, it takes time for the kidney to adjust and to stop losing normal amounts of potassium ions. In the meantime, a deficit may be created. In addition, renal conservation mechanisms cannot completely eliminate potassium excretion, so that 5-10 mEq/day is lost regardless of total body deficit.

Endocrinopathies. These conditions are discussed in detail elsewhere. Patients with primary aldosteronism (Conn’s syndrome) are hypokalemic in about 80% of cases. Patients with secondary aldosteronism (cirrhosis, malignant hypertension, renal artery stenosis, increased estrogen states, hyponatremia) are predisposed toward hypokalemia. Cirrhosis may coexist with other predisposing causes, such as poor diet or attempts at diuretic therapy. About 20%-25% of patients with Cushing’s syndrome have a mild hypokalemic alkalosis. Congenital adrenal hyperplasia (of the most common 11-b-hydroxylase type) is associated with hypokalemia. Hypokalemia may occur in Bartter’s syndrome or the very similar condition resulting from licorice abuse. Most of the conditions listed in this section, except for cirrhosis, are also associated with hypertension.

Severe trauma. In a review of three studies of trauma patients, hypokalemia was much more common (50%-68% of patients) than hyperkalemia. Hypokalemia usually began within 1 hour after the trauma and usually ended within 24 hours.

Diabetic ketoacidosis. Extracellular fluid (ECF) may lose potassium both from osmotic diuresis due to hyperglycemia and from shift of extracellular to intracellular potassium due to insulin therapy. Nevertheless, these changes are masked by dehydration, so that 90% of patients have normal or elevated serum potassium values when first seen in spite of substantial total body potassium deficits. These deficits produce overt hypokalemia if fluid therapy of diabetic acidosis does not contain sufficient potassium.

Hypokalemic alkalosis. Hypokalemia has a close relationship to alkalosis. Increased plasma pH (alkalosis) results from decreased ECF hydrogen ion concentrations; the ECF deficit draws hydrogen from body cells, leading to decreased intracellular concentration and therefore less H+ available in renal tubule cells for exchange with urinary sodium. This means increased potassium excretion in exchange for urinary sodium and eventual hypokalemia. Besides being produced by alkalosis, hypokalemia can itself lead to alkalosis, or at least a tendency toward alkalosis. Hypokalemia results from depletion of intracellular potassium (the largest body store of potassium). Hydrogen ions diffuse into body cells to partially replace the intracellular cation deficit caused by potassium deficiency; this tends to deplete ECF hydrogen levels. In addition, more hydrogen is excreted into the urine in exchange for sodium since the potassium that normally would participate in this exchange is no longer available. Both mechanisms tend eventually to deplete extracellular fluid hydrogen. As noted in Chapter 24, in alkalosis due to hypokalemia an acid urine is produced, contrary to the usual situation in alkalosis. This incongruity is due to the intracellular acidosis that results from hypokalemia.

Medication-induced hypokalemia. Certain non-diuretic medications may sometimes produce hypokalemia. Ticarcillin, carbenicillin, and amphotericin B may increase renal potassium loss. Theophylline, especially in toxic concentration, may decrease serum potassium to hypokalemic levels.

In one group of hospitalized patients with serum potassium levels less than 2.0 mEq/L, apparent etiology was potassium-insufficient IV fluids in 17%, diuretic therapy in 16%, GI loss in 14%, acute leukemia receiving chemotherapy in 13%, dietary potassium deficiency in 6%, renal disease with urinary potassium loss in 6%, diabetic acidosis in 5%, and all other single causes less than 5% each.

Urine potassium assay in hypokalemia

Measurement of urine potassium may sometimes be useful in differentiating etiologies of hypokalemia. Those conditions associated with decreased urine potassium include the following:

1. Loss from the GI tract (diarrhea, villous adenoma, ileal conduit). Vomiting, however, is associated with alkalosis, which may increase renal potassium excretion.
2. Shift of extracellular potassium to intracellular location (insulin therapy). However, hyperglycemic osmotic diuresis may confuse the picture.
3. Inadequate potassium intake, in the absence of conditions that increase urine potassium excretion.
4. Potassium deficiency associated with renal excretion of potassium (e.g., diuretic induced) after the stimulus for potassium loss is removed and renal loss ceases.

Besides the first three categories, the other etiologies for hypokalemia usually demonstrate normal or increased urine potassium levels while active potassium loss is occurring.